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176 papers

Tri-Parametric Assessment of α-Galactosidase A Activity, lysoGb3 and X-Inactivation Aids Genotype-Phenotype Categorization of Fabry Disease Female Patients.

Kuchar L et al. · Jul 1, 2026

Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disorder caused by deficient activity of lysosomal alpha-galactosidase A (AGAL, E.C. 3.2.1.22) due to pathogenic variants in the GLA gene (HGNC:4296, Xq22.1). Plasmatic deacylated globotriaosylceramide (lysoGb3) is elevated in FD patients as a reflection of lysosomal accumulation of Gb3. Specific (AGALopathic) GLA variants have been recently shown to accumulate within the secretory pathway and trigger endoplasmic reticulum stress and unfolded protein response rather than result in profound enzymatic deficiency. In part due to lack of integrative measures of clinical severity and biochemical/molecular parameters, specific impacts and consequences of X-chromosomal inactivation (XCI) on clinical manifestation in FD female heterozygotes still remain to be fully understood. Our study aimed at evaluation of XCI (% of inactive wt GLA allele) in untreated female FD heterozygotes with classic FD (n = 17), late-onset FD (n = 19) and individuals carrying GLA variants (p.(L394P) (n = 7), p.(A143T) (n = 4), and p.(D313Y) (n = 4)) with predominant AGALopathic effects. XCI was correlated with age of the patients, clinical phenotype, (residual) AGAL activity, and lysoGb3. AGAL activity corresponded to XCI independently of the type of the GLA mutation. The best separation of the clinical phenotypes (classic FD, late-onset FD and AGALopathy) was achieved by correlating XCI to the ratio of AGAL activity to lysoGb3. This three parametric calculated marker was then confronted with the Mainz Severity Score Index (MSSI) to generate an Integrative Clinical-Laboratory quotient (ICLq). ICLq discriminated the three female patient groups and demonstrated group-dependent differences in its average age-related increase.

Medicine

Fall risk assessment scale for hemodialysis patients (ERQUE_HD): development and validation.

Farina VA et al. · Jul 1, 2026

Introduction Hemodialysis patients present multiple comorbidities and complications during therapy, factors that increase the risk of falls. Adequate risk assessment is essential for implementing effective preventive measures. Objective To develop and validate a scale for assessing fall risk in hemodialysis patients. Method A methodological study with quantitative and qualitative approaches, conducted in five stages: integrative review, focus groups, instrument development, content validation, and scale validation. Results The integrative review included 17 articles and supported the initial item development. Nine focus groups with patients and healthcare professionals enabled the identification of additional risk factors, resulting in the construction of the ERQUE_HD (Fall Risk Assessment Scale for Hemodialysis Patients), composed of 17 items distributed across four domains: health history, dialysis-related factors, functional capacity, and nutrition. Content validation reached a content validity index (CVI) of 0.95, considered highly satisfactory. The scale was then applied to 66 patients and analyzed using logistic regression with generalized estimating equations (GEE), including variables such as post-dialysis fatigue, interdialytic weight gain, and intradialytic hypotension. Patients classified as high-risk were 8.7 times more likely to experience falls compared to the moderate-risk group. The ERQUE-HD demonstrated good accuracy (AUC = 0.817). Post-dialysis fatigue and interdialytic weight gain >4% were identified as significant fall predictors. Conclusion The ERQUE-HD proved to be effective in assessing and predicting fall risk among hemodialysis patients.

Medicine

Dietary Phytochemical Index and Its Relationship With Diminished Ovarian Reserve: Evidence From a Case-Control Study.

Khodarahmi M et al. · Jul 1, 2026

Introduction Diminished ovarian reserve (DOR) represents a significant contributor to female infertility and adverse reproductive outcomes. Although diet may play a role, the specific impact of phytochemical-rich dietary patterns remains underexplored. So, we aimed to investigate the association between adherence to a dietary phytochemical index (DPI) and the likelihood of DOR among women attending fertility clinics. Methods This case-control study enrolled 370 women, comprising 120 individuals diagnosed with DOR and 250 age- and body mass index (BMI)-matched controls with normal ovarian reserve. A validated semi-quantitative food frequency questionnaire (FFQ) was applied to assess dietary intakes and, accordingly, DPI was calculated as the proportion of total energy intake obtained from phytochemical-abundant foods. Antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) measurements were utilized as indicators of ovarian reserve. The association between DPI and the odds of DOR was investigated using multivariable logistic regression models. Results Our findings showed that higher DPI was associated with a reduced odds of DOR (Q4 vs. Q1 OR: 0.79; 95% CI: 0.55-0.93; p-trend = 0.010). After adjustment for physical activity and energy intake, the association remained significant (OR: 0.80; 95% CI: 0.54-0.95; p-trend = 0.033). In the fully adjusted model, which included additional adjustments for fat mass and body mass index, women in the highest DPI quartile had 27% lower odds of DOR compared to those in the lowest quartile (OR: 0.73; 95% CI: 0.42-0.97; p-trend = 0.02). Besides, in the control group, AFC differed significantly across DPI quartiles (p Conclusion Our findings suggest that a phytochemical-rich diet may help reduce the odds of DOR, highlighting the role of diet in reproductive health. However, further prospective studies and mechanistic research are warranted to confirm these results and clarify underlying pathways.

Medicine

Validation of an automated chromogenic in situ hybridization protocol for detection of cytomegalovirus in formalin-fixed, paraffin-embedded renal graft biopsies.

Rangel JV et al. · Jul 1, 2026

Introduction Histopathological diagnosis of human cytomegalovirus (HCMV) infection in formalin-fixed, paraffin-embedded (FFPE) tissues stained with hematoxylin-eosin relies on the identification of characteristic cytopathic changes, including eosinophilic intranuclear and cytoplasmic viral inclusions. Chromogenic in situ hybridization (CISH) enables the localization of specific nucleic acid sequences in histological sections, increasing diagnostic sensitivity. Automated CISH platforms allow standardized and reproducible detection of viral RNA or DNA in FFPE tissues. This study aimed to validate an automated CISH protocol for the detection of HCMV in multiple tissue types, including renal allograft biopsies processed at the Anatomical Pathology Division of UERJ. Methods Two groups of FFPE samples were analyzed. The first group included ten samples from various tissues, including kidney, palate, esophagus, stomach, and colon; nine positive and one negative for HCMV by immunohistochemistry (IHC). The second group included twenty renal allograft biopsies; nineteen without previous diagnosis and one positive by IHC. For CISH, fluorescein-conjugated oligonucleotide probes targeting HCMV RNA expressed during the early replication phase were used, with hybridization and detection performed on an automated platform. Results In Group 1, all samples, including the case previously negative by IHC, were positive for HCMV by CISH. In Group 2, six of the twenty renal biopsies were positive, including the sample already identified as positive by IHC. Conclusions The automated CISH protocol demonstrated high sensitivity and reproducibility for HCMV detection, supporting its validation and use in the diagnosis of renal biopsies and other tissues, as well as its incorporation into the routine workflow of Anatomical Pathology laboratories.

Medicine

The Staging Model in Psychosis and Preventive Interventions: An Emerging Field With Debates on Conceptual Models and Interpretation of the Evidence Base.

van der Gaag M et al. · Jul 1, 2026

Aims The staging model in psychiatry is heuristic and evolving, provoking debate and stimulating alternative views. This paper reviews major controversies in the field of staging and prevention of psychosis. Methods We review the literature on the classification model, the continuum model and the dynamic systems model applied to psychiatry. Other controversies are stigmatisation of early detection, the prevention paradox and the interpretation of data on prevention of transition to psychosis. Results DSM classifications still lack validity. The continuum model supports preclinical stages but has no discrete conversions to different stages of illness. The emerging dynamic systems model builds on the interaction of symptoms eliciting networks of symptoms, while at the same time it explains sudden catastrophic shifts (transitions) between different states of equilibrium. Stigmatisation of early psychosis can be balanced against the benefits of early interventions. The prevention paradox states that only a minority of first episode cases arises from the high-risk group. However, there are many reasons to combine indicated prevention with population-based preventive interventions. A long-lasting controversy is on the interpretation of the research data. Several meta-analyses are reviewed on methodological issues. Conclusion The staging model is adequate to conceptualise psychiatric disorders and the progress over time in more chronic stages. No one is suggesting that help-seeking patients with an ARMS should be denied access to psychosocial treatment and it is recommended and necessary to continue building age and stage specific services to treat them and continue with research into risk factors and helpful interventions.

Medicine

Effectiveness of Alcohol Use Disorder Pharmacotherapies by Sex: Systematic Review and Meta-Analysis.

Allen J et al. · Jul 1, 2026

Issues Alcohol use disorder (AUD) shows sex-related differences in prevalence, harm and treatment response. Despite growing interest in sex differences, evidence synthesis evaluating pharmacotherapy effectiveness by sex remains limited. Approach Web of Science, PubMed, Scopus, PsycINFO and Cochrane were searched twice. Eligible records included RCTs or non-randomised studies of adults with AUD receiving pharmacological interventions (licensed or off-label), and reporting or providing outcomes (binary relapse or continuous alcohol consumption change) by sex. Multi-level random-effects models calculated risk ratios (RR) and standardised mean differences (SMD), with sex as a moderator. Key findings Twenty-eight studies (25,041 participants, 25% female) were included. No outcomes were rated low risk of bias; non-RCTs were moderate-to-high quality. Overall treatment effects vs. control were small for abstinence (RR = 0.96, 95% CI [0.52, 1.74]; 4 studies; I 2 = 95%) and modest for consumption reduction (SMD = 0.23, 95% CI [0.01, 0.45]; 13 studies; I 2 = 89%); sex did not meaningfully moderate these outcomes (ratio of RR = 1.04, 95% CI [0.87, 1.25]; ΔSMD = 0.05, 95% CI [-0.09, 0.18]). Power was low (median 13.7%), requiring ~6358 participants per group to detect the observed sex difference. Narrative synthesis suggested possible sex differences for naltrexone and baclofen, while highlighting the influence of drug (e.g., tolerability), participant (e.g., drinking motives) and design factors (e.g., recruitment setting) on treatment response. Implications AUD pharmacotherapies provide modest benefits, with sex differences remaining unclear. Future trials should be adequately powered, report sex-specific outcomes and consider adherence, tolerability and psychosocial moderators. Conclusion Evidence for sex-specific efficacy remains inconclusive. Patterns for naltrexone and baclofen warrant exploration in large, rigorously designed, sex-stratified trials.

Medicine

Systematic Review of Intravenous Ceftriaxone Administration in Animals.

de Vasconcelos PMF et al. · Jul 1, 2026

Background Ceftriaxone is an antibiotic frequently prescribed in veterinary medical practice due to its effectiveness against several pathogenic microorganisms responsible for diseases in different animal species. Objective To select scientific articles from the academic databases PubMed and Web of Science that analysed the pharmacokinetic aspects of intravenously administered ceftriaxone in animals. Methods In accordance with the principles of scientific transparency, the systematic review protocol and all research stages were previously registered on the Open Science Framework (OSF) platform. The scientific articles that met the inclusion criteria were subjected to a checklist comprising 24 minimum assessment items designed for reporting pharmacokinetic studies. Results A total of 52 pharmacokinetic profiles were identified from the 29 selected scientific articles, including records involving 13 different animal species used in ceftriaxone experimental studies. Conclusion The limitations and inconsistencies identified in this review highlight the importance of detailed reporting of pharmacokinetic data derived from experimental trials in animals.

Medicine

Methanol intoxication and acute kidney injury: pathophysiological mechanisms and therapeutic approaches.

Nogueira GN et al. · Jul 1, 2026

Methanol intoxication is a potentially lethal condition that primarily affects the central nervous system, but it can also induce significant renal damage. Acute kidney injury (AKI) in this context is often underestimated, despite being an important prognostic marker associated with increased mortality and morbidity. This review aims to elucidate the pathophysiological mechanisms linking methanol intoxication to AKI, describe the cellular and metabolic pathways involved, and discuss current therapeutic approaches for renal protection and recovery. A descriptive and analytical review was conducted through searches in the PubMed, Embase, and Cochrane Library databases, including studies published between 2000 and 2025. Eligible articles addressed methanol-related nephrotoxicity, AKI mechanisms, or treatment strategies involving fomepizole, hemodialysis, and renal support. The nephrotoxic effects of methanol are mediated by the accumulation of formic acid, which inhibits mitochondrial cytochrome oxidase, leading to tissue hypoxia, oxidative stress, and cellular apoptosis. The main renal alterations include osmotic nephrosis and acute tubular necrosis, frequently associated with metabolic acidosis, rhabdomyolysis, or hemolysis. Risk factors such as anemia, sepsis, volume depletion, and acute pancreatitis exacerbate renal injury. AKI is linked to higher rates of multiple organ failure and in-hospital mortality. Methanol-induced AKI results from multifactorial mechanisms involving mitochondrial dysfunction, oxidative stress, and hemodynamic instability.

Medicine

Long-Term Cardiometabolic Outcomes in Children With Metabolically Healthy and Unhealthy Obesity.

Putri RR et al. · Jul 1, 2026

Importance Metabolically healthy obesity (MHO) in children has been considered a low-risk phenotype, potentially not requiring treatment. However, their long-term cardiometabolic outcomes remain unclear. Objective To compare the occurrence of type 2 diabetes, hypertension, dyslipidemia, and mortality up to young adulthood in children with metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), and general population peers, and to investigate the association between obesity treatment response and disease risk. Design, setting, and participants This was a prospective cohort study including children undergoing obesity treatment recorded in the Swedish Childhood Obesity Treatment Register (BORIS) between 1997 and 2020 and their general population comparators, linked with national registers. Children in the cohort with obesity were aged 7 to 17 years at obesity treatment initiation and had complete cardiometabolic data. General population comparators were matched (ratio 1:5) based on sex, birth year, and residential area. Study data were analyzed from February to March 2025. Exposures Exposures included metabolically healthy obesity (MHO), defined as the absence of high blood pressure, impaired fasting glycemia, elevated transaminases, elevated triglycerides, and low high-density lipoprotein cholesterol; otherwise, children were categorized as having metabolically unhealthy obesity (MUO). Main outcomes and measures Type 2 diabetes, hypertension, dyslipidemia, and mortality up to age 30 years. Results A total of 7275 children (median [first quartile {Q1}-third quartile {Q3}] age, 11.1 [9.1-13.5] years; 4004 male [55.0%]) were included, along with 35 636 general population comparators (median [Q1-Q3] age, 11.1 [9.1-13.5] years; 19 596 male [55.0%]). MHO at baseline was present in 3626 children (49.8%; median [Q1-Q3] age, 10.6 [8.8-12.8] years; 1981 male [54.6%]), and MUO was present in 3649 children (50.2%; median [Q1-Q3] age, 11.6 [9.4-14.0] years; 2023 male [55.4%]). By age 30 years, cumulative incidences were as follows: type 2 diabetes (MHO, 9.1%; MUO, 16.8%; general population, 0.5%), hypertension (MHO, 10.8%; MUO, 18.3%; general population, 3.7%), and dyslipidemia (MHO, 5.3%; MUO, 12.7%; general population, 0.9%). A reduction of at least 0.25 body mass index (BMI) z score was associated with reduced incidence rate ratio (IRR) of type 2 diabetes (IRR, 0.22; 95% CI, 0.14-0.35), hypertension (IRR, 0.56; 95% CI, 0.34-0.93), and dyslipidemia (IRR, 0.28; 95% CI, 0.14-0.57), with similar risk reduction for MHO and MUO. Conclusions and relevance Results of this cohort study reveal that a reduction in BMI z score of at least 0.25 was associated with similar risk reductions for both MHO and MUO. Children with MHO face a substantially increased cardiometabolic disease risk already as young adults compared with the general population. Hence, obesity treatment should be recommended for all children with obesity, regardless of initial metabolic status.

Medicine

Acute Effect of Percussive Massage on Cross-Section Area, Muscle Strength, and Late Muscle Pain of the Quadriceps Muscle Following a Fatigue Protocol in Physically Active Men: Randomized Clinical Trial.

da Rosa Castilho A et al. · Jul 1, 2026

Background and purpose The massage gun is widely used to alleviate delayed-onset muscle soreness (DOMS); however, empirical evidence regarding its physiological effects remains limited. Objectives This study aimed to evaluate the acute effects of percussive massage on the quadriceps muscle's cross-sectional area (CSA), strength performance, and pain perception following a fatigue protocol. Methods A randomized clinical trial was conducted including 37 physically active men. Participants performed a fatigue protocol on a 45° leg press, at 70% of their one-repetition maximum (1RM). The volunteers were allocated to an intervention group (G0 n = 19, mean ± SD; 25.7 ± 4.5 years, 83.7 ± 10.6 kg, 176.8 ± 6.3 cm) and control group (G1 n = 18, mean ± SD; 27.6 ± 5.0 years, 76.8 ± 15.7 kg, 174 ± 7.3 cm). Assessments were performed at baseline, 24 and 48 h, using ultrasound imaging, isometric dynamometer and VAS questionnaire (visual analog pain scale). Results Regarding the muscle area, significant increases were observed in the control group p 2.0) in strength maintenance at 24 and 48 h compared to G1. Both groups showed reduction in pain over time, while G0 demonstrated a significant decrease at 48 h compared to 24 h (53%, p Conclusion Within-group assessments revealed significant reductions in pain perception over time for the intervention group. Regarding muscle strength, despite a large exploratory effect size observed during recovery, no statistically significant between-group superiority over passive rest was established. The findings suggest potential preliminary benefits for symptom relief without acute performance deficits.

Medicine